The endothelium plays a critical role in promoting inflammation in cardiovascular disease and other chronic inflammatory conditions, and many small molecule screens have sought to identify agents that prevent endothelial cell activation. Conversely, an augmented immune response can be protective against microbial pathogens and in cancer immunotherapy. Yet, small molecule screens to identify agents that induce endothelial cell activation have not been reported. Small molecules for endothelial cell activation are thus limited.
On the other hand, to interrogate small molecule libraries, high-throughput screening (HTS) systems that detect compounds with pre-specified molecular targets have been developed. However, a limitation of most current screens is that they do not integrate the interactions that occur between heterogeneous cell types involved in disease pathogenesis-they are a severe oversimplification. This has resulted in a conceptual shift towards “systems biology” approaches, which, because of their increased complexity, are more difficult to automate for HTS. Therefore, a significant need exists for screening systems that can link a compound's molecular structure with biological function and gene expression in adequately complex systems.
The embodiments described below address the above mentioned issues and problems.